Roh Tae-Young, Cuddapah Suresh, Zhao Keji
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Genes Dev. 2005 Mar 1;19(5):542-52. doi: 10.1101/gad.1272505. Epub 2005 Feb 10.
The identity and developmental potential of a human cell is specified by its epigenome that is largely defined by patterns of chromatin modifications including histone acetylation. Here we report high-resolution genome-wide mapping of diacetylation of histone H3 at Lys 9 and Lys 14 in resting and activated human T cells by genome-wide mapping technique (GMAT). Our data show that high levels of the H3 acetylation are detected in gene-rich regions. The chromatin accessibility and gene expression of a genetic domain is correlated with hyperacetylation of promoters and other regulatory elements but not with generally elevated acetylation of the entire domain. Islands of acetylation are identified in the intergenic and transcribed regions. The locations of the 46,813 acetylation islands identified in this study are significantly correlated with conserved noncoding sequences (CNSs) and many of them are colocalized with known regulatory elements in T cells. TCR signaling induces 4045 new acetylation loci that may mediate the global chromatin remodeling and gene activation. We propose that the acetylation islands are epigenetic marks that allow prediction of functional regulatory elements.
人类细胞的身份和发育潜能由其表观基因组决定,表观基因组在很大程度上由包括组蛋白乙酰化在内的染色质修饰模式所定义。在此,我们通过全基因组图谱技术(GMAT)报告了静息和活化的人类T细胞中组蛋白H3赖氨酸9和赖氨酸14双乙酰化的高分辨率全基因组图谱。我们的数据表明,在基因丰富的区域检测到高水平的H3乙酰化。一个遗传域的染色质可及性和基因表达与启动子和其他调控元件的高乙酰化相关,但与整个域普遍升高的乙酰化无关。在基因间和转录区域鉴定出乙酰化岛。本研究中鉴定出的46813个乙酰化岛的位置与保守非编码序列(CNSs)显著相关,其中许多与T细胞中已知的调控元件共定位。TCR信号诱导4045个新的乙酰化位点,这些位点可能介导全局染色质重塑和基因激活。我们提出,乙酰化岛是表观遗传标记,可用于预测功能性调控元件。